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For infants born significantly before term, enteral supplementation with omega-3 fatty acid docosahexaenoic acid (DHA) at best did not prevent bronchopulmonary dysplasia (BPD) and at worst may even cause harm, according to a meta-analysis.

Across four studies, high-dose DHA wasn't significantly linked to BPD when administered to neonatal infants born prior to 29 weeks (RR 1.07, 95% CI 0.86-1.34). Further analysis also showed no association with combined BPD or death (RR 1.04, 95% CI 0.91-1.18) at 36 weeks' postmenstrual age, reported Isabelle Marc, MD, PhD, of Centre Hospitalier Universitaire de Québec-Université Laval, and coauthors.

On the other hand, high-dose DHA supplementation was linked to excess events when using the more stringent definition of physiological BPD plus mortality (RR 1.11, 95% CI 1.02-1.20). Additionally, the intervention was associated with a significantly increased risk of BPD in studies where systematic oximetry data were available for these newborns (RR 1.20, 95% CI 1.01-1.42), according to the meta-analysis published in .

Similar findings were observed tying high-dose DHA supplementation and moderate-to-severe BPD (RR 1.16, 95% CI 1.04-1.29).

"Based on the current available evidence on BPD, high-dose enteral DHA supplementation during the neonatal period cannot be recommended for prevention of BPD in very preterm infants. Additionally, the use of DHA supplements by mothers who provide their own breast milk to their very preterm infants cannot be recommended for prevention of BPD," Marc's group wrote.

"However, more studies are needed to understand the mechanisms involved, as DHA was expected to play a role in the reduction of oxidative stress and inflammation underlying the pathogenesis of BPD," the authors noted.

Their study aimed to provide clear recommendations after analyzing that provided conflicting or inconsistent results on DHA and its potential impact on BPD in infants. Previous systematic reviews had focused on BPD in infants up to 32 weeks' gestational age and had varying inclusion criteria, DHA intervention doses, and cointerventions such as respiratory care management, according to Marc and colleagues.

The authors acknowledged that the small number of trials available for analysis limit the findings of their own meta-analysis, while the fact that the locations of the trials, which were in countries with access to neonatal care, limit their results' applicability. They encouraged further research.

"Beyond the clinical significance of the association of DHA with short-term neonatal outcomes, long-term follow-up of these cohorts is required because the potential benefits for long-term neurodevelopment and cardiorespiratory health would need to be balanced against the potential increased risk of BPD," they wrote.

"In addition to these research recommendations, documenting the dose-response associations between lipids metabolism and outcomes will contribute to overall health improvement in very preterm infants by implementing better practices in neonatal nutrition," they added.

The meta-analysis included four studies covering a population of 2,304 preterm infants with an average 26.5 weeks' gestational age.

For infants receiving high-dose DHA supplementation, the supplements were administered either through enriched breast milk, or directly to the child. The DHA used in the study came from algal oils, fish oils, or a combination of arachidonic acid with sunflower, algal, or fungal oils.

These newborns were compared against controls who received standard care only or placebo with no or a low-dose of DHA supplementation, defined as less than 40 mg/kg per day administered directly or less than 0.4% of total fatty acids in formula or breast milk.

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